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Dietary Supplements: A Framework for Evaluating Safety
those formed in humans, the results are less meaningful and testing in species with metabolism similar to humans should be considered.
Genetic, reproductive, developmental, immunological, neurobiological, and behavioral toxicity studies, as well as other types of studies, provide further information regarding the toxicity of the test substance.
Safety Pharmacology Studies
Safety pharmacology studies are conducted in various animal species to detect alterations in physiological functions at dosages lower than those used to elicit overt toxic effects detected in animal toxicity protocols. Guidance for conducting safety pharmacology studies for human pharmaceuticals is provided by FDA, which defines them as “those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above” (ICH/FDA, 2001). Safety pharmacology testing generally focuses on endpoints that differ from those examined in classic toxicity testing. The studies may be in vivo or in vitro and are designed to detect harmful effects in a core battery of vital organ systems, which include the cardiovascular, central nervous, and respiratory systems.
Observations from Veterinary Medicine
Veterinary toxicological observations may also prove useful in predicting the potential effect of dietary supplement ingredients on humans. The discipline of veterinary medicine/toxicology encompasses the entire spectrum of effects of natural and synthetic toxins, including drugs, pesticides, herbicides, and fungal and plant metabolites, on wildlife, livestock, and domestic animals (i.e., pets). The specific subdiscipline best described as plant-associated veterinary toxicology is likely to correlate most closely with adverse effects of botanical-derived dietary supplement ingredients. It is distinguished from toxicological studies in that it is primarily observational information or is based on studies not designed to predict effects on human health. Nevertheless, there are numerous examples of incidents of animal poisoning that have subsequently led to epidemiological studies and ultimately controlled experiments that resulted in identification of specific toxins and their mode of action. The well-known cases of aflatoxin-induced poultry toxicity led to the controlled animal and epidemiological studies that resulted in the classification of this important fungal metabolite as a human carcinogen (Mishra and Das, 2003).
An advantage of considering plant-associated animal toxicity observations in livestock is that episodes of poisoning often occur on a large scale, affecting tens or even hundreds of animals, so that there is little doubt as to